Our aims are to understand the mechanisms of tumor cell adhesion and invasion and to define the metabolic pathways that regulate these processes. We have demonstrated that cis-polyunsaturated fatty acids stimulate adhesion of human breast tumor cells through a pathway that involves MAP kinases, protein kinases C, and b1 integrins. We have identified a MAP kinase, p38, as a specific protein that is phosphorylated during the activation of adhesion in these cells by the fatty acids. Furthermore, we have shown that two isozymes, epsilon and mu, in the novel class of protein kinase C enzymes are translocated to membrane fractions in response to exposure of breast tumor cells to a dietary fatty acid. These enzymes are critical for adhesion and spreading of breast tumor cells on type IV collagen. We have also shown that dietary fatty acids induce changes in the localization of key cytoskeletal proteins, such as filamentous actin, vinculin, and a-actinin, and increase the colocalization of b1 integrins with these proteins. We are currently working to identify other members of signal transduction pathways whose activity is regulated by these fatty acids and to determine how these signals lead to changes in the cytoskeleton and, ultimately, in cell behaviors such as migration and invasion.